rs1053320

Positions:

chr21-46003722-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001848.3(COL6A1):c.2796C>T(p.Ser932Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,612,542 control chromosomes in the GnomAD database, including 68,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7820 hom., cov: 35)

Exomes 𝑓: 0.29 ( 61014 hom. )

Consequence

COL6A1
NM_001848.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -4.25

Variant links:

Genes affected

COL6A1 (HGNC:2211): (collagen type VI alpha 1 chain) The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy. [provided by RefSeq, Jul 2008]

COL6A1 links:

COL6A1 (HGNC:):

COL6A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 21-46003722-C-T is Benign according to our data. Variant chr21-46003722-C-T is described in ClinVar as [Benign]. Clinvar id is 93870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46003722-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A1	NM_001848.3 linkuse as main transcript	c.2796C>T	p.Ser932Ser	synonymous_variant	35/35	ENST00000361866.8	NP_001839.2	P12109A0A384P5H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8 linkuse as main transcript	c.2796C>T	p.Ser932Ser	synonymous_variant	35/35	1	NM_001848.3	ENSP00000355180.3		P12109

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47410

AN:

152144

Hom.:

7813

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.267

AC:

66141

AN:

247462

Hom.:

9322

AF XY:

0.261

AC XY:

35097

AN XY:

134618

show subpopulations

Gnomad AFR exome

AF:

0.406

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.147

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.286

AC:

417096

AN:

1460280

Hom.:

61014

Cov.:

AF XY:

0.282

AC XY:

204625

AN XY:

726430

show subpopulations

Gnomad4 AFR exome

AF:

0.414

Gnomad4 AMR exome

AF:

0.286

Gnomad4 ASJ exome

AF:

0.220

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.296

Gnomad4 OTH exome

AF:

0.267

GnomAD4 genome

AF:

0.312

AC:

47448

AN:

152262

Hom.:

7820

Cov.:

AF XY:

0.309

AC XY:

22999

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.409

Gnomad4 AMR

AF:

0.313

Gnomad4 ASJ

AF:

0.220

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.251

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.297

Hom.:

4177

Bravo

AF:

0.321

Asia WGS

AF:

0.176

AC:

617

AN:

3478

EpiCase

AF:

0.281

EpiControl

AF:

0.278

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 17, 2012	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 22, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Bethlem myopathy 1A

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Collagen 6-related myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Ullrich congenital muscular dystrophy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.038

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over